Biography

I have been a member of the Harvard Medical School community as a student, clinician, researcher, and teacher. My current roles include Staff Anesthesiologist at MGH, Investigator on several NIH-sponsored basic research grants, Reviewer for NIH grants (Surgery Anesthesia and Trauma study section), Member of the DACCPM Research Council, Subcommittee Chair for HST medical admissions, Co-director of the Harvard Anesthesia Research Training Fellowship (T32), Co-director of HST150 (Principles of Clinical Pharmacology), and member of several scientific committees of the American Society of Anesthesiologists. I am a Professor of Anaesthesiology at Harvard Medical School and an Anesthetist at MGH.

Research Areas

Description of Research

My research aims are to understand where and how general anesthetics act at the molecular level in order to help design better drugs for use in clinical settings. The molecular targets studied are anesthetic sensitive pentameric ligand-gated ion channels, including g-aminobutyric acid-A (GABAA), glycine, nicotinic acetylcholine, and serotonin receptors. Of greatest interest are potent intravenous agents including etomidate, propofol, alphaxalone, and barbiturates. We express cloned channels in cells and use electrophysiological methods to study channel function. We developed a unique 'artificial synapse' technique for high-resolution kinetic studies. Based on an allosteric co-agonist mechanism that we established for etomidate and propofol, we conduct structure-function studies in mutant receptors. We are also mapping out binding sites for anesthetics using substituted cysteine accessibility methods that combine electrophysiology with real-time chemical modification of receptors. In collaboration with Keith Miller, DPhil and Doug Raines, MD, my group also contributes to research on new photo-reactive general anesthetics, production of GABAA receptor protein for photolabeling, and development of new general anesthetics for clinical use.